Resveratrol reduction of infarct size in Long-Evans rats subjected to focal cerebral ischemia

Although vasomotion has been considered a feature of the microvascular bed under physiological conditions, it has also been observed following hypotension in several tissues. In this work, 158 mesenteric microvessels of 36 rats were investigated quantitatively in normovolemic and hemorrhaged animals, focussing on diameter changes, particularly vasomotion incidence and characteristics. The femoral arteries of Wistar rats (body weight BW = 188 +/- 23 g, mean +/- SD) anesthetized with pentobarbital were cannulated for arterial pressure (AP) monitoring and blood withdrawal. The protocol consisted of 15 min control and 30 min of hemorrhagic hypotension (AP = 52 +/- 5 mmHg, hemorrhaged vol. = 17 +/- 4 ml/kg BW). During control normovolemic conditions, analysis of mesenteric microcirculation using intravital videomicroscopy revealed neither arteriolar nor venular vasomotion. During hemorrhagic hypotension (HH) microvascular blood flow reduced to 25% of control. While venules did not show diameter changes during HH, arterioles contracted to 85 +/- 20% of control and arteriolar vasomotion appeared in 42% of the animals and 27% of the arterioles. The amplitude of arteriolar diameter change during HH relative to mean diameter and to control diameter averaged 65 +/- 24% (range: 32-129%) and 41 +/- 10% (range: 25-62%), respectively. Vasomotion analysis showed two major frequency components: 1.7 +/- 0.8 and 7.0 +/- 5.2 cycles/min. Arterioles showing vasomotion had a mean control diameter larger than the remaining arterioles and showed the largest constriction during HH. We conclude that hemorrhagic hypotension does not change venular diameter but induces arteriolar constriction and vasomotion in rat mesentery. This activity is expressed as slow waves with high amplitude and fast waves with low amplitude, and is dependent on vessel size.     

Role of gastric microcirculation in the gastroprotection by glucocorticoids released during water-restraint stress in rats

Our previous investigations demonstrated that glucocorticoids released in response to stress protect gastric mucosa against stress-induced ulceration. This study was designed to determine whether gastric microcirculation is involved in the mechanism of gastroprotective glucocorticoid action. For this we evaluated the effects of deficiency of glucocorticoid production during 3 hr water-restraint stress and corticosterone replacement on the stress-induced gastric erosions, gastric microcirculation and arterial pressure in rats. The stress was produced in awake rats and gastric microcirculation and arterial pressure were evaluated in animals anesthetized in 3 hr after the onset of water-restraint stress. An in vivo microscopy technique for the direct visualization of gastric microcirculation was employed. The gastric submucosal and the superficial mucosal microvessels were monitored on television screen through a microscope and the pictures were stored by microfilming for the analysis of red blood cell velocity and vessel diameter. Gastric microcirculation was estimated on the base of both the volume blood flow velocity in submucosal microvessels and the diameter of superficial mucosal venous microvessels. Gastric erosions were quantitated by measuring the area of damage. Plasma corticosterone levels were also measured after 3 hr stress by fluorometry. Water-restraint stress induced an increase in corticosterone level, an appearance of gastric erosions, a decrease in volume blood flow velocity of submucosal microvessels, a dilatation of superficial mucosal microvessels, a decrease in arterial pressure. The deficiency of glucocorticoid production during water-restraint stress promoted the stress-induced gastric ulceration, a dilatation of mucosal microvessels, a decrease of blood flow velocity in submucosal microvessels and of arterial pressure. Corticosterone replacement eliminated the effects of deficiency of glucocorticoid production on all of the parameters under study. Thus, the stress-induced corticosterone rise decreased gastric ulceration, restricted both the reduction of blood flow velocity in submucosal microvessels and a dilatation of superficial mucosal venous microvessels during water-restraint stress. These data suggest that the gastroprotective action of glucocorticoids during stress may be provided by the maintenance of gastric blood flow.     

Vasomotion: the case for chaos

Fluctuations in vascular calibre, a phenomenon known as vasomotion, are ubiquitous in the microcirculation and represent emergent behaviour that involves synchronisation of Ca²⁺ oscillations in individual vascular cells. Ideally, coordinated interactions between locally generated vasomotion and neuro-humoral control mechanisms will allow optimal sensing of flow and pressure within vascular networks and thereby facilitate synergistic readjustments in local vascular conductance and flow under conditions of dynamically changing metabolic demand. Indeed, many studies have reported that vasomotion becomes more prominent under pathophysiological conditions, suggesting that it may serve as an adaptive homeodynamic response that maintains or re-establishes flow when perfusion is compromised. We here summarise evidence that the apparent irregular nature of vasomotion reflects deterministic interactions between a small number of dominant control variables, rather than random events, and may therefore be formally classified as chaotic. We also discuss the potential physiological benefits of chaos in the microcirculation and the key roles of signalling via gap junctions and nitric oxide.     

The rate of O₂ loss from mesenteric arterioles is not unusually high

The O(2) disappearance curve (ODC) recorded in an arteriole after the rapid arrest of blood flow reflects the complex interaction among the dissociation of O(2) from hemoglobin, O(2) diffusivity, and rate of respiration in the vascular wall and surrounding tissue. In this study, the analysis of experimental ODCs allowed the estimation of parameters of O(2) transport and O(2) consumption in the microcirculation of the mesentery. We collected ODCs from rapidly arrested blood inside rat mesenteric arterioles using scanning phosphorescence quenching microscopy (PQM). The technique was used to prevent the artifact of accumulated O(2) photoconsumption in stationary media. The observed ODC signatures were close to linear, in contrast to the reported exponential decline of intra-arteriolar Po(2). The rate of Po(2) decrease was 0.43 mmHg/s in 20-μm-diameter arterioles. The duration of the ODC was 290 s, much longer than the 12.8 s reported by other investigators. The arterioles associated with lymphatic microvessels had a higher O(2) disappearance rate of 0.73 mmHg/s. The O(2) flux from arterioles, calculated from the average O(2) disappearance rate, was 0.21 nl O(2)·cm(-2)·s(-1), two orders of magnitude lower than reported in the literature. The physical upper limit of the O(2) consumption rate by the arteriolar wall, calculated from the condition that all O(2) is consumed by the wall, was 452 nl O(2)·cm(-3)·s(-1). From consideration of the microvascular tissue volume fraction in the rat mesentery of 6%, the estimated respiration rate of the vessel wall was ～30 nl O(2)·cm(-3)·s(-1). This result was three orders of magnitude lower than the respiration rate in rat mesenteric arterioles reported by other investigators. Our results demonstrate that O(2) loss from mesenteric arterioles is small and that the O(2) consumption by the arteriolar wall is not unusually large.     

Visualization and Analysis of Blood Flow and Oxygen Consumption in Hepatic Microcirculation: Application to an Acute Hepatitis Model

There is a considerable discrepancy between oxygen supply and demand in the liver because hepatic oxygen consumption is relatively high but about 70% of the hepatic blood supply is poorly oxygenated portal vein blood derived from the gastrointestinal tract and spleen. Oxygen is delivered to hepatocytes by blood flowing from a terminal branch of the portal vein to a central venule via sinusoids, and this makes an oxygen gradient in hepatic lobules. The oxygen gradient is an important physical parameter that involves the expression of enzymes upstream and downstream in hepatic microcirculation, but the lack of techniques for measuring oxygen consumption in the hepatic microcirculation has delayed the elucidation of mechanisms relating to oxygen metabolism in liver. We therefore used FITC-labeled erythrocytes to visualize the hepatic microcirculation and used laser-assisted phosphorimetry to measure the partial pressure of oxygen in the microvessels there. Noncontact and continuous optical measurement can quantify blood flow velocities, vessel diameters, and oxygen gradients related to oxygen consumption in the liver. In an acute hepatitis model we made by administering acetaminophen to mice we observed increased oxygen pressure in both portal and central venules but a decreased oxygen gradient in the sinusoids, indicating that hepatocyte necrosis in the pericentral zone could shift the oxygen pressure up and affect enzyme expression in the periportal zone. In conclusion, our optical methods for measuring hepatic hemodynamics and oxygen consumption can reveal mechanisms related to hepatic disease.     

Contribution of vasomotion to vascular resistance: a comparison of arteries from virgin and pregnant rats

Intrinsic oscillatory activity, or vasomotion,within the microcirculation has many potential functions, includingmodulation of vascular resistance. Alterations in oscillatory activityduring pregnancy may contribute to the marked reduction in vascularresistance. The purpose of this study was1) to mathematically model theoscillatory changes in vessel diameter and determine the effect onvascular resistance and 2) tocharacterize the vasomotion in resistance arteries of pregnant andnonpregnant (virgin) rats. Mesenteric arteries were isolated fromSprague-Dawley rats and studied in a pressurized arteriograph.Mathematical modeling demonstrated that the resistance in a vessel withvasomotion was greater than that in a static vessel with the same meanradius. During constriction with the₁-adrenergic agonistphenylephrine, the amplitude of oscillation was less in the arteriesfrom pregnant rats. We conclude that vasomotor activity may provide amechanism to regulate vascular resistance and blood flow independent ofstatic changes in arterial diameter. During pregnancy the decrease invasomotor activity in resistance arteries may contribute to thereduction in peripheral vascular resistance.

     

快速减压对豚鼠外周微循环和大脑血流量的影响

目的：探讨动物处于减压病（ＤＣＳ）临界发病状态时微及其血流动力作用的改变。方法：采用小型化激光微综在数测量仪及ＬＤＦ－３微区血流量仪,以检测动物高压暴露前及快速减压后微循环和血流动力作用的改变。结果：快速减压后动物微血管明显收缩;毛细血管开放数量减少;微循环中可见气泡并有血栓形成;白细胞、血小板与血管内皮粘附;血流中有料多白色微小血栓;细动脉血流速度平均比正常状态减慢０．９ｍｍ／ｓ,细静脉流速减慢     

Network thermodynamic analysis of vasomotion in a microvascular network.

The modulation of microvascular blood flow by vasomotion in the individual vessels of a simple vascular network was simulated by means of a network thermodynamic model. The flow is driven under a pulsating pressure through two arcades of branching vasoactive arterioles into a passive resistance representing the capillary and venular beds. Each vessel was assumed to have the capability of decreasing rhythmically the local diameter over a short section by a specified fraction of the maximum value and to change the average diameter along its total length in response to alterations in intraluminal pressure. Blood was assumed to exhibit a simple linear viscous flow resistance. Alterations in flow rate and distribution through the network were determined as a function of the magnitude and frequency of vasomotion within the individual arterioles supplying blood to the microvascular bed. Specific cases are shown to illustrate how blood flow can be influenced by the patterns of vasomotion within the network.     

Effect of low-intensity He-Ne laser irradiation on rat mesenteric microcirculation

Changes in microcirculation during low-intensity He-Ne laser irradiation were studied by measurement of blood vessels and lymphangions' diameter in anesthetized rat mesentery using method of videomicroscopy in vivo. We demonstrated that the red coherent light induced a significant increase in contractility of vessels' smooth muscle cells. The flow decreased in the mesenteric microvessels during H2O2-mediated oxidant stress was restored after He-Ne laser irradiation.     

Use of the television analysing system in the studies on microcirculation]

In the experiments on anesthetized rats the television analysing system (LEITZ-TAS) was used for evaluation of quantitative structure-functional characteristics of microcirculation under intravital conditions and the development of microvessel network, for measuring geometric parameters of microvessels and blood flow change in them, as well as to define the degree and spreading of the disturbances in the vessel wall permeability.     

Fiberoptic laser-doppler anemometer microscope applied to the cerebral microcirculation in rats

We have applied our developed fiber-optic laser-Doppler anemometer microscope (FLDAM) for the study of the cerebral microcirculation in the rat. The red cell velocity in single pial microvessels was successfully measured through a closed cranial window for the vessel diameter range from 7.8 to 230 μm. The temporal resolution of the FLDAM was sufficiently high to detect the pulsation in the arterioles. Arterio-venous distributions of the temporal mean red cell velocity and wall shear rate are also described.     

小鼠急性低氧暴露时脑微循环障碍的研究

本研究旨在通过急性减压缺氧状态下脑微循环改变的观察进一步探讨急性高原病的发生机理。实验采用鼠尾静脉注射吖啶橙荧光素作标记,落射荧光显微镜观察分析。结果表明,急性低氧状态下脑血管普遍扩张,但脑表面微血管的扩张大于脑深部微血管的扩张,微动脉的扩张大于微静脉的扩张;脑表面及深部的毛细血管开放数目增多、密度增加、间距缩小;脑血流随缺氧加重而变慢并有淤积;微血管周围有渗出及出血;神经细胞肿胀,胞浆内有空泡水肿。提示急性高原缺氧状态下脑微循环有明显障碍。     

Effects of flowing RBCs on adhesion of a circulating tumor cell in microvessels

Adhesion of circulating tumor cells (CTCs) to the microvessel wall largely depends on the blood hydrodynamic conditions, one of which is the blood viscosity. Since blood is a non-Newtonian fluid, whose viscosity increases with hematocrit, in the microvessels at low shear rate. In this study, the effects of hematocrit, vessel size, flow rate and red blood cell (RBC) aggregation on adhesion of a CTC in the microvessels were numerically investigated using dissipative particle dynamics. The membrane of cells was represented by a spring-based network connected by elastic springs to characterize its deformation. RBC aggregation was modeled by a Morse potential function based on depletion-mediated assumption, and the adhesion of the CTC to the vessel wall was achieved by the interactions between receptors and ligands at the CTC and those at the endothelial cells forming the vessel wall. The results demonstrated that in the microvessel of \(15\,\upmu \hbox {m}\) diameter, the CTC has an increasing probability of adhesion with the hematocrit due to a growing wall-directed force, resulting in a larger number of receptor–ligand bonds formed on the cell surface. However, with the increase in microvessel size, an enhanced lift force at higher hematocrit detaches the initial adherent CTC quickly. If the microvessel is comparable to the CTC in diameter, CTC adhesion is independent of Hct. In addition, the velocity of CTC is larger than the average blood flow velocity in smaller microvessels and the relative velocity of CTC decreases with the increase in microvessel size. An increased blood flow resistance in the presence of CTC was also found. Moreover, it was found that the large deformation induced by high flow rate and the presence of aggregation promote the adhesion of CTC.     

Regional myocardial O2 consumption and coronary blood flow responses to acetylcholine in rabbit heart

The effect of acetylcholine on regional coronary blood flow and myocardial O2 consumption was determined in order to compare its direct vasodilatory effects with the metabolic vasoconstriction it induces. Experiments were conducted in seven untreated control anaesthetized open chest rabbits and seven rabbits which were infused with acetylcholine (1 microgram/kg/min). Myocardial blood flow was determined before and during acetylcholine infusion using radioactive microspheres. Regional arterial and venous O2 saturation was analyzed microspectrophotometrically. Acetylcholine reduced heart rate by 30% and significantly depressed the arterial systolic and diastolic blood pressure. The mean O2 consumption was significantly reduced with acetylcholine from 9.6 +/- 2.0 to 6.1 +/- 3.6 ml O2/min/100 g. Coronary blood flow decreased uniformly across the left ventricular wall by about 50% and resistance to flow increased by 42% despite potential direct cholinergic vasodilation. O2 extraction was not affected by acetylcholine infusion. It is concluded that the acetylcholine infusion directly decreased myocardial O2 consumption, which in turn lowered the coronary blood flow and increased the resistance. The decreased flow was related to a reduced metabolic demand rather than a direct result of lowered blood pressure. Unaffected myocardial O2 extraction also suggested that blood flow and metabolism were matched. This indicates that direct cholinergic vasodilation of the coronary vasculature does not allow a greater reduction in metabolism than flow in the anaesthetized open chest rabbit heart during acetylcholine infusion.     

The Open Microcirculation in Human Spleens: A Three-Dimensional Approach

It has long been debated whether the red pulp of human spleens harbors an open or a closed microcirculation or both. To solve this issue, the authors differentially stained the endothelium in red pulp arterial microvessels and in venous sinuses using brightfield and fluorescence immunohistology with reagents against CD34 and CD141. Three-dimensional models of red pulp arterial microvessels and sinuses were derived from serial double-stained paraffin sections with the help of license-free open-access software. In each model, arterial microvascular ends were traced and verified by reference to the original serial sections. In total, 142 ends were analyzed in the specimens of three individuals. None of these ends was connected to a sinus, suggesting that the human splenic red pulp harbors an entirely open circulatory system. Thus, the spleen is the only human organ where blood passes through spaces not lined by endothelia or other barrier-forming cells.     

Vasomotion and neurovascular coupling in the visual thalamus in vivo

Spontaneous contraction and relaxation of arteries (and in some instances venules) has been termed vasomotion and has been observed in an extensive variety of tissues and species. However, its functions and underlying mechanisms are still under discussion. We demonstrate that in vivo spectrophotometry, measured simultaneously with extracellular recordings at the same locations in the visual thalamus of the cat, reveals vasomotion, measured as an oscillation (0.14 hz) in the recorded oxyhemoglobin (OxyHb) signal, which appears spontaneously in the microcirculation and can last for periods of hours. During some non-oscillatory periods, maintained sensory stimulation evokes vasomotion lasting ~30s, resembling an adaptive vascular phenomenon. This oscillation in the oxyhaemoblobin signal is sensitive to pharmacological manipulation: it is inducible by chloralose anaesthesia and it can be temporarily blocked by systemic administration of adrenaline or acetylcholine (ACh). During these oscillatory periods, neurovascular coupling (i.e. the relationship between local neural activity and the rate of blood supply to that location) appears significantly altered. This raises important questions with regard to the interpretation of results from studies currently dependent upon a linear relationship between neural activity and blood flow, such as neuroimaging.     

Dynamic viscous flow in distensible vessels of skeletal muscle microcirculation: application to pressure and flow transients

Blood flow in the microcirculation of the rat skeletal muscle during transient changes of arterial pressure is analyzed theoretically. Although flow in such small vessels is quasi-steady and has a very low Reynolds number, time-dependent nonuniform flows along the length of the blood vessels can be observed due to vessel distensibility. The governing equations for a single microvessel are derived using previously measured microvessel elasticity, and several solutions to different inflow and outflow pressures and flow conditions are investigated. The results indicate that when such distensible microvessels are subjected to a step increase of arterial pressure, the arterial flow shows a rapid overshoot followed by a progressive decay to steady-state. An arterial step flow induces a different response which takes the form of a monotonically increasing pressure. Pressure and flows are nonuniform along the vessel length during such transients. In-vitro whole organ pressure-flow data are presented in the dilated rat gracilis muscle which qualitatively agree with the theoretical predictions.     

Effects of desensitization of capsaicin-sensitive afferent neurons on gastric microcirculation in rats depend on the blood glucocorticoid hormone level

The effects of desensitization of capsaicin-sensitive afferent neurons on gastric microcirculation were investigated before and after administration of indomethacin at ulcerogenic dose in adrenalectomized rats with or without corticosterone replacement and in sham-operated animals. We estimated the blood flow velocity in submucosal microvessels; the diameters and permeability of mucosal venous microvessels as parameters of gastric microcirculation. Desensitization of capsaicin-sensitive neurons was performed with capsaicin at the dose 100 mg/kg two weeks before the experiment. Adrenalectomy was created one week before experiment. In vivo microscopy technique for the direct visualization of gastric microcirculation and the analysis of the blood flow was employed. Indomethacin at ulcerogenic dose decreased the blood flow velocity in submucosal microvessels, caused dilatation of superficial mucosal microvessels and increased their permeability. Desensitization of capsaicin-sensitive afferent neurons potentiated indomethacin-induced microvascular disturbances in gastric submucosa-mucosa. These potentiated effects of the desensitization are obviously promoted by concomitant glucocorticoid deficiency. Thus, glucocorticoid hormones have a beneficial effect on gastric microcirculation in rats with desensitization of capsaicin-sensitive afferent neurons.     

Mechanical behavior of the erythrocyte in microvessel stenosis

The passage of red blood cells (RBCs) through capillaries is essential for human blood microcirculation. This study used a moving mesh technology that incorporated leader-follower pairs to simulate the fluid-structure and structure-structure interactions between the RBC and a microvessel stenosis. The numerical model consisted of plasma, cytoplasm, the erythrocyte membrane, and the microvessel stenosis. Computational results showed that the rheology of the RBC is affected by the Reynolds number of the plasma flow as well as the surface-to-volume ratio of the erythrocyte. At a constant inlet flow rate, an increased plasma viscosity will improve the transit of the RBC through the microvessel stenosis. For the above reasons, we consider that the decreased hemorheology in microvessels in a pathological state may primarily be attributed to an increase in the number of white blood cells. This leads to the aggregation of RBCs and a change in the blood flow structure. The present fundamental study of hemorheology aimed at providing theoretical guidelines for clinical hemorheology.     

Microcirculatory hematocrit and blood flow

Direct measurements from many laboratories indicate that the oxygen tension in skeletal muscle is significantly less than in the large veins draining these tissues. Harris (1986) has proposed that because of the parallel anatomic arrangement of large arterioles and venules in skeletal muscle, a counter-current exchange between these vessels can occur. He theorized that diffusion of O2 between arteriole and venule would lower the PO2 in the blood as it enters capillaries and result in a decreased tissue PO2 and an increase in large vein PO2. Calculations (Appendix) show that the amount of O2 transferred between arteriole and venule is inadequate to account for this difference in PO2 between tissue and veins due to the small surface area that is involved. It is well documented that the microcirculatory hematocrit ranges between 20 and 50% of that in the supply vessels. The reduced hematocrit lowers the oxygen content in these vessels and results in a low oxygen tension in the surrounding tissue. True arteriovenous shunts are not present in most skeletal muscles, but 15-20% of the microvessels represent thoroughfare or preferential flow channels. It is suggested that these vessels contain a greater than normal hematocrit to account for a conservation of red cell mass across the microcirculation. Furthermore, it is shown that the hematocrit in the preferential flow channels is an inverse function of the flow rate for any level of the microcirculatory hematocrit. The increased hematocrit raises the flow resistance in these vessels which reduces flow further and represents a positive feedback condition which may contribute to the intermittent and uneven flow patterns which are present within the microcirculation.(ABSTRACT TRUNCATED AT 250 WORDS)